Certain 2-iminothiazole phosphates and phosphonates

ABSTRACT

COMPOUNDS OF THE FORMULA   2-(R2-P(=S)(-R3)-S-CH2-CO-N=),3-R4,4-R,5-R1-2,3-DIHYDRO-   THIAZOLE   IN WHICH R IS HYDROGEN OR ALKYL, R1 IS HYDROGEN OR ALKYL, R2 IS ALKYL OR ALKOXY, R3 IS ALKOXY, R4 IS ALKYL, ALKENYL, ALKYNYL, BENZYL OR CARBAMOYLOXYALKYLENE AND THE USE OF THESE COMPOUNDS AS INSECTICIDES AND ACARICIDES.

Unitcd States Patent ABSTRACT OF THE DISCLOSURE Compounds of the formula R -N-R4 I i/ R1 S N'-C'-CH2SP\ ii R3 in which R is hydrogen or alkyl; R is hydrogen or alkyl; R is alkyl or alkoxy; R is alkoxy; R is alkyl, alkenyl,

alkynyl, benzyl or carbamoyloxyalkylene and the use of these compounds as insecticides and acaricides.

This invention relates to certain novel heterocyclic chemical compounds and their use as insecticide and acaricides. More particularly, the compounds are certain S-N-substituted thiazole phosphates and phosphonates.

The compounds of this invention that are useful as insecticides and acaricides are those having the formula:

in which R is hydrogen or alkyl having 1 to 5 carbon atoms, inclusive, preferably methyl; R is hydrogen or alkyl having 1 to 5 carbon atoms, inclusive, preferably methyl; R is alkyl having 1 to 5 carbon atoms, inclusive, or alkoxy having 1 to 5 carbon atoms, inclusive; R is al'koxy having 1 to 5 carbon atoms, inclusive; R is alkyl having 1 to '5 carbon atoms, inclusive, preferably 1 to 3 carbon atoms, inclusive, alkenyl having 3 to 6 carbon atoms, inclusive, preferably 3 carbon atoms, alkynyl having 3 to 6 carbon atoms, inclusive, preferably 3 carbon atoms, benzyl, or carbamoyloxyalkylene, wherein said alkylene has 1 to 3 carbon atoms, inclusive, preferably 2 carbon atoms.

The compounds having the formula in which R, R R R and R are as defined above can be prepared by the following reactions:

R sLNH NH4X F H2O 3 ,729,478 Patented Apr. 24, 1973 ICC Equation (c), the reaction of the haloacetamide with the phosphono or phosphoro dithioic acid is an in situ reaction between a haloacetamide with a salt of an organic phosphate or phosphonate. The reaction of a base .1101

and dimethylformamide (DMF) as a solvent medium which facilitates and promotes the reaction.

.Although other solvents such as ketones, alcohols, benzone-H O mixtures, etc., can be used, DMF has been found most advantageous with regard to reaction times and yields. It has also been found that a small excess of triethylamine is advantageous in bringing the reaction to completion.

After completion of the reaction between the chloroacetamide and the phosphate, or phosphonate amine salt, the product is conveniently isolated by pouring the mixture into Water. .If the product is a solid, it is filtered off and recrystallized if desired. If the product is a liquid, it can be extracted with a solvent such as benzene, chloroform, etc.

Chloroacetamide derivatives are used for economic reasons; however, bromo or iodoacetamides can also be used.

The compounds of the present invention and their preparation are more particularly illustrated by the following examples. Following the example is a table of compounds which are prepared according to the procedures described herein.

EXAMPLE Preparation of the intermediate 2-imino-3-N-methylthiazole.Fifty grams (50 g., 0.5 mole) of Z-aminothiazole, 78.1 g. (0.55 mole) of methyl iodide in 100 cc. of methanol were mixed and refluxed for 2 hours. The reaction mixture was cooled to 15 C. and filtered. The solid material was slurried in ether, filtered and washed with hexane. There was obtained 91.9 g. of product. The filtrate was evaporated, slurried in cc. of boiling isopropanol, cooled and filtered. Total yield was 106.2 g. (87.6% of theory).

The solid product, supra, was dissolved in water (300 cc.). Concentrated ammonium hydroxide (40.5 g., 0.66 mole, 45 cc.) was added while maintained at a temperature below 20 C. The reaction mixture was exhaustively extracted with chloroform, dried over anhydrous magnesium sulfate, filtered and the organic solvent evaporated in vacuo. There was obtained 41.9 g. (84% of theory) of the title compound. n =1.59l5.

Preparation of the intermediate 2-chloroacetylimino-3 -N-methylthiazole.The intermediate 2-imino-3-N-methylthiazole (41.9 g., 0.37 mole) was added to a solution of chloroacetic anhydride (82 g., 0.48 mole) in dioxane (80 cc.). The temperature during the addition was maintained below 65 C. After addition was completed, the reaction mixture was heated to 65- 72 C. for minutes. It was cooled to 60 C. and 10 ml. of water added, cooled to 45 C. and ice water added. The product was filtered and washed with ice water and dried. There was obtained 42.8 g. (71.8% of theory) of the title compound, M.P. 117-120 C.

Preparation of 2-0,0-diethylphosphorodithioyl acetimino-3N-methylthiazole.-Eleven and four-tenths grams (0.06 mole) of 2-chloroacetylimino-3-N-methylthiazole was slurried in ml. of DMF to this stirred mixture was added a pre-neutralized mixture of 18.6 g. (0.1 mole) (16.4 ml.) of 0,0-diethylphosphorodithioic acid dissolved in 30 ml. DMF and 10.1 g. (0.1 mole) (13.8 ml.) of triethylamine. To this stirred mixture was added an additional 2 ml. of triethylamine to make the mixture basic. The mixture was heated and stirred at 55-60 C. for two hours. After the completion of the reaction, 150-200 ml. of benzene was added and the mixture washed twice with dilute sodium chloride solution, dried over anhdyrous magnesium sulfate, filtered, and the benzene evaporated. There was obtained 19.5 g. (95.6% of theory) of the title compound, a liquid, n =l.5896.

The above structure was confirmed by N.M.R. and infrared analysis.

The following is a table of compounds which are prepared according to the aforementioned procedures. Compound numbers have been assigned to them and are used for identification throughout the balance of the specification.

4 INSECTICIDAL EVALUATION TESTS The term insect is used herein in its broad common usage to include spiders, mites, ticks and like pests which are not in the strict biological sense classified as insects. The term insect is used to refer not only to those small invertebrate animals belonging mostly to the class Insecta, comprising six-legged usually winged forms, as beetles, bugs, bees, flies, and so forth, but also to other allied classes of arthropods whose members are Wingless and usually have more than six legs, as spiders, mites, ticks, centipedes, and wood lice.

The following insect species were used in evaluation tests for insecticidal activity:

(1) Housefly (HF)-Musca domestica (Linn.) (2) Lygus bug (LB)Lygus hesperus (Knight) (3) Bean aphid (BA)-Aphis fabae (Scop.)

The housefly (HF) was used in evaluation tests of selected compounds as insecticides by the following procedure. A stock solution containing 100 ,ug./ml. of the toxicant in an appropriate solvent was prepared. Aliquots of this solution were combined with 1 milliliter of an acetone-peanut oil solution in a glass petri dish and allowed to dry. The aliquots were there to achieve desired toxicant concentration ranging from 100 ,ug./per petri dish to that at which mortality was attained. The petri dishes were placed in a circular cardboard cage, closed on the bottom with cellophane and covered on top with cloth netting. Twenty-five female houseflies, three to five days old, were introduced into the cage and the percent mortality was recorded after 48 hours. The LD-50 values are expressed in terms of ,ug. per 25 female flies. The results of this insecticidal evaluation test are given in Table II under HF.

In the lygus bug (LB) Lygus hesperus test, ten to twenty-five two-week old nymphs of lygus bug were placed in separate circular cardboard cages sealed on one end with cellophane and covered by a cloth netting on the other. Aliquots of the toxicants, dissolved in an appro- M.P., Compound or 1112 number R R R R3 R4 kal.

H CC2H5 OC2H5 CH3 1. 5896 H C2H5 O CzH5 CH3 1. 6109 H O C2H5 O CzHs CH 94-95 CH3 0 02115 0 02115 CH3 117-120 H C2H5 0 021215 CH3 50-53 CH3 C2H5 O CzH5 CH3 -77 H CzHs 0 CH(CH3) CH3 106-108 CH3 C2115 0CH(CH3)2 CH3 99-101 H C2H5 OCH(CH3)2 CH3 1. 5968 CH C2115 OCHzCH(CHa)2 CH3 68-70 H CH3 0 CH3 CH3 97 H OOHQ OCH: CH3 1. 5944 H C2H5 0 CH3 CH3 1. 6199 H OCHa OCHa CH2CH=CH2 1. 5907 H C2H5 OCH(CH3)2 CH2CH=CH2 1. 5863 H C2115 OC H CHgCH=CHz 1. 5352 H C2H5 0 CH3 CH2CH=CH2 1- 5874 H 02115 O C2H5 CH 205011 52-54 H C2H5 CCH(CH3)2 CHzCECH 54-56 H CzHa OCHa CH2CECH 1. 6186 H C2H OCHCH2(CHa)2 CHZCECH 1. 5823 H C2115 O CzH5 1. 6146 23 H H C2115 OCH(CH;) 1. 6112 24 H H OCzH5 0C2H5 1. 6035 H CzH5 0 CHaCHKCHa) a 1. 5997 H CzH4 O CH(CH9)2 CHBCHZCH: 1. 5550 H 02135 O CH (CH3) 2 0 78-82 priate solvent, were diluted in water containing 0.002% of a wetting agent, Sponto 221 (polyoxyether of alkylated phenols blended with organic sulfonates). Test concentrations ranged from 0.05% downward to that at which 50% mortality was obtained. Each of the aqueous suspensions of the candidate compounds were sprayed onto the insect through the cloth netting by means of a hand-spray gun. Percent mortality in each case recorded after 24 and 72 hours counts Were made to determine living and dead insects. The LD-50 values eX- pressed as percent of toxicant in the aqueous spray were calculated and recorded. These values are reported under the column LB in Table II.

The insect species black bean aphid (BA) A phis faba'e (Scop.) was also employed in the test for insecticidal activity. Young nasturtium (Tropaeolum sp.) plants, ap proximately 2 to 3 inches tall, were used as the host plants for the bean aphid. The host plant was infeste d with approximately 5075 of the aphids. The test chemical was dissolved in acetone, added to Water which contained a small amount of Sponto 22l, an emulsifying agent. The solution was applied as a spray to the infested plants. Concentrations ranged from 0.05 percent downward until an LD-50 values was achieved. These results are given in Table 11 under the column BA.

ACARICIDAL EVALUATION TEST The two-spotted mite (ZSM), T etranychus urticae (Koch), was employed in tests for miticides. Young pinto bean plants or lima bean plants (Phaseolus sp.) in the primary leaf stage were used as the host plants. The young pinto bean plants were infested with about 100 mites of various ages. Dispersions of candidate materials were prepared by dissolving 0.1 gram in ml. of a suitable solvent, usually acetone. Aliquots of the toxicant solutions were suspended in water containing 0.002% v./v. Sponto 221, polyoxyethylene ether sorbitan monolaurate, an emulsifying agent, the amount of water being suflicient to give concentrations of active ingredient ranging from 0.05% to that at which 50% mortality was obtained. The test suspensions Were then sprayed on the infested plants to the point of run off. After 7 days, mortalities of the post-embryonic form was determined. The percentage of kill was determined by comparison with control plants which had not been sprayed with candidate compounds. The LD50 value was calculated using well-known procedures. These values are reported under the columns 2SM-PE and ZSM-Eggs, in Table II.

SYSTEMIC EVALUATION TEST This test evaluates the root absorption and upward translocation of the candidate systemic compound. The bean aphid (BA) A phis fabae (Scop.) was employed in the test for systemic activity.

Young nasturtium plants were used as the host plants for the bean aphid. The host plants were transplated into one pound of soil that had been treated with the candidate compound. Immediately after planting in the treated soil, the plants were infested with the aphids. Concentrations of toxicant in the soil ranged from 10 p.p.m. per pound of soil downward until an LD50 value was obtained. Mortality was recorded after 72 hours.

The percentage of kill of the test species was determined by comparison with control plants placed in distilled water or untreated soil. The LD50 values were calculated. These systemic test results are reported in Table II under the column BA-SYS.

TABLE II 2SM, percent Compound HF, LB, BA, BA-sys., number |Lg./25% percent percent p.p.m. PE Eggs NoTn.(-indicates not tested for the indicated insect species.)

The candidate compounds were also tested as systemic toxicants against two-spotted mite according to the following procedure.

Aliquots of the toxicant dissolved in an appropriate solvent are diluted in water and placed in glass bottles. Concentrations of active ingredient range from 10 p.p.m. to that at which 50% mortality is obtained. Pinto bean (Phaseolus sp.) plants with expanded primary leaves are placed in the solution so that the roots and major portions of the stern are completely immersed. Immediately after, the leaves are infested with 75l00 mites of various ages. Mortality of adults, nymphs and eggs is recorded after one week, and LD-50 values are expressed as parts per million (p.p.m.) of toxicant in the aqueous suspensions.

Some of the results as a systemic toxicant against twospotted mite, can be summarized as follows: Compound No. l, LD-SO: 10 p.p.m.; and Compound No. 2, LD50: 1 p.p.m.

As those in the art are well aware, various techniques are available for incorporating the active component or toxicant in suitable pesticidal compositions. Thus, the pesticidal compositions can be conveniently prepared in the form of liquids or solids, the latter preferably as homogeneous free-flowing dusts commonly formulated by admixing the active component with finely divided solids or carriers as exemplified by talc, natural clays, diatomaceous earth, various flours such as walnut shell, wheat, soya bean, cottonseed and the like.

Liquid compositions are also useful and normally comprise a dispersion of the toxicant in a liquid media although it may be convenient to dissolve the toxicant directly in a solvent such as kerosene, fuel oil, xylene, alkylated naphthalenes or the like and use such organic solutions directly. However, the more common procedures is to employ dispersions of the toxicant in an aqueous medium and such compositions may be produced by forming a concentrated solution of the toxicant in a suitable organic solvent followed by dispersion in water, usually with the aid of surface active agents. The latter, which may be anionic, cationic or nonionic types, are exemplified by sodium stearate, potassium oleate and other alkaline metal soaps and detergents such as sodium lauryl sulfate, sodium naphthalene sulfonate, sodium alkyl naphthalene sulfonate, methyl cellulose, fatty alcohol ethers, polyglycol fatty acid esters, and other polyoxyethylene surface active agents. The proportion of these agents commonly comprises 1-15% by Weight of the pesticidal compositions although the proportion is not critical and may be varied to suit any particular situation.

7 What is claimed is: 1. A compound of the formula in which R is hydrogen or alkyl having 1 to carbon atoms, inclusive; R is hydrogen or alkyl having 1 to 5 carbon atoms, inclusive; R is alkyl having 1 to 5 carbon atoms, inclusive, or alkoxy having 1 to 5 carbon atoms, inclusive; R is alkoxy having 1 to 5 carbon atoms, inclusive; R is alkyl having 1 to 5 carbon atoms, inclusive, alkenyl having 3 to 6 carbon atoms, inclusive, alkynyl having 3 to 6 carbon atoms, inclusive, benzyl, or carbamoyloxyalkylene, wherein said alkylene has 1 to 3 carbon atoms, inclusive.

2. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, inclusive, R is alkoXy having 1 to 5 carbon atoms, inclusive, and R is alkyl having 1 to 5 carbon atoms, inclusive.

3. The compound according to claim 2 in which R is ethoxy, R is ethoxy and R is methyl.

4. The compound according to claim 2 in which R is methoxy, R is methoxy and R is methyl.

5. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, and R is alkyl having 1 to 5 carbon atoms, inclusive.

6. The compound according to claim 5 in which R is ethyl, R is ethoxy and R is methyl.

7. The compound according to claim 5 in which R is ethyl, R is isopropoxy and R is methyl.

8. The compound according to claim 5 in which R is methyl, R is methoxy and R is methyl.

9. The compound according to claim 5 in which R is ethyl, R is methoxy and R is methyl.

10. The compound according to claim 5 in which R is ethyl, R is isopropoxy and R is n-propyl.

11. A compound according to claim 1 in which R is alkyl having 1 to 5 carbon atoms, inclusive, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, and R is alkyl having 1 to 5 carbon atoms, inclusive.

12. The compound according to claim 11 in which R is methyl, R is ethoxy, R is ethoxy and R is methyl.

13. A compound according to claim 1 in which R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, R is alkoXy having 1 to 5 carbon atoms, inclusive and R is alkyl having 1 to 5 carbon atoms, inclusive.

14. The compound according to claim 13 in which R is methyl, R is methyl, R is ethoxy, R is ethoXy and R is methyl.

15. A compound according to claim 1 in which R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms and R is alkyl having 1 to 5 carbon atoms, inclusive.

16. The compound according to claim 15 in which R is methyl, R is methyl, R is ethyl, R is ethoxy and R is ethyl.

17. The compound according to claim 15 in which R is methyl, R is methyl, R is ethyl, R is isopropoxy and R is methyl.

18. The compound according to claim 15 in which R is methyl, R is methyl, R is ethyl, R is isobutyl and R is methyl.

19. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive and R is alkenyl having 3 to 6 carbon atoms, inclusive.

20. The compound according to claim 19 in which R; is methoxy, R is methoxy and R is Z-propenyl.

21. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive and R is alkenyl having 3 to 6 carbon atoms, inclusive.

22. The compound according to claim 21 in which R is ethyl, R is isopropoxy and R is 2-propenyl.

23. The compound according to claim 21 in which R is ethyl, R is ethoxy and R is 2-propenyl.

24. The compound according to claim 21 in which R is ethyl, R is methoxy and R is 2-propenyl.

25. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, and R is alkynyl having 3 to 6 carbon atoms, inclusive.

26. The compound according to claim 25 in which R is ethyl, R is ethoxy and R is 2-propynyl.

27. The compound according to claim 25 in which R is ethyl, R is isopropoxy and R is 2-propynyl.

28. The compound according to claim 25 in which R is ethyl, R is methoxy and R is 2-propynyl.

2.9. The compound according to claim 25 in which R is ethyl, R is isobutoXy and R is 2-propynyl.

30. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkoxy having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive and R is benzyl.

31. The compound according to claim 30 in which R is ethoxy and R is ethoxy.

32. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, and R is benzyl.

33. The compound according to claim 32 in which R; is ethyl and R is ethoxy.

34. The compound according to claim 32 in which R is ethyl and R is isopropoxy.

35. The compound according to claim 32 in which R is ethyl and R is isobutoxy.

36. A compound according to claim 1 in which R is hydrogen, R is hydrogen, R is alkyl having 1 to 5 carbon atoms, inclusive, R is alkoxy having 1 to 5 carbon atoms, inclusive, and R is carbamoyloxyalkylene wherein said alkylene has 1 to 3 carbon atoms, inclusive.

37. The compound according to claim 36 in which R is ethyl, R is isopropyl and R is N-methylcarbamoyloxyethylene.

References Cited UNITED STATES PATENTS 3,591,600 7/1971 Fancher 260-3068 R ALEX MAZEL, Primary Examiner R. I. GALLAGHER, Assistant Examiner US. Cl. X.R. 260943; 424-200 

